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The standard regimens for graft-versus-host disease (GvHD) prophylaxis in matched unrelated donor (MUD) transplantation were based on antithymocyte globulin (ATG) in combination with calcineurin inhibitors (CNIs). To improve the efficiency of GvHD prophylaxis in MUD peripheral blood stem cell transplantation (MUD-PBSCT), 51 patients with hematological malignancies received a novel regimen for GvHD prophylaxis, which is composed of low dose of ATG (5 mg/kg) plus low-dose posttransplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF). The cumulative incidences (CIs) of grades I–IV and II–IV acute GvHD (aGvHD) were 14.5% (95% CI, 9.4–19.6%) and 6.2% (95% CI, 2.8–9.6%) within 100 days after transplantation, respectively. The CI of mild-to-moderate chronic GvHD (cGvHD) within 1 year was 11.5% (95% CI, 6.6–16.4%). The 1-year probabilities of GvHD and relapse-free survival, relapse-free survival, and over survival were 70.6% (95% CI, 64.2–77.0%), 76.5% (95% CI, 70.6–82.4%), and 82.0% (95% CI, 76.5–87.5%), respectively. The CIs of CMV and EBV reactivation by day 180 were 10.4% (95% CI, 1.5–19.4%) and 8.3% (95% CI, 0.2–16.4%), respectively. The results suggested that low-dose ATG/PTCy combined with CsA/MMF as GvHD prophylaxis in MUD-PBSCT had promising activity.

Purpose Studies have shown an increased risk for mortality in patients with psoriasis. Furthermore, research has demonstrated an inverse relationship between 25-hydroxyvitamin D (25[OH]D) level and all-cause mortality. This study investigated the association between 25(OH)D level and all-cause mortality in US adults with psoriasis. Methods Data from NHANES (1999–2014 and mortality data through December 31, 2015) were analyzed. Quartiles of 25(OH)D level were created based on 25(OH)D levels among patients. Cox proportional hazards models were used for estimating hazard ratios (95% CI) for all-cause mortality. Findings A total of 82,091 participants were enrolled in the NHANES study from 1999 to 2014. Overall, 610 patients with psoriasis were identified in NHANES. The mean (SD) duration of follow-up was 5.61 (3.38) years (3427.92 person-years). The hazard ratio for mortality in the fully adjusted model was 0.12 (95% CI, 0.02–0.60; Ptrend = 0.01) in patients with a high 25(OH)D concentration compared to those with 25(OH)D deficiency. Implications The 25(OH)D concentration was significantly inversely associated with all-cause mortality among these patients with psoriasis. Studies have shown an increased risk for mortality in patients with psoriasis compared to the general population. Vitamin D is not regularly metabolized in patients with psoriasis due to their skin abnormality. Vitamin D supplementation has been associated with a reduced mortality in patients with psoriasis. In practice, attention to vitamin D level is crucial, as is the use of vitamin D supplementation, for improving the health of these patients.

Background Myocardial infarction (MI) is the most common cause of cardiovascular morbidity and mortality worldwide. Despite the identification of many pathogenic genes associated with MI, the underlying molecular mechanisms remain poorly understood. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. Pyroptosis is a caspase-1-dependent pro-inflammatory programmed cell death (PCD) mechanism. The role of pyroptosis in several diseases associated with various miRNAs has been studied extensively. Meanwhile, the role of NOD-like receptor-containing pyrin 3 (NLRP3)/caspase-1/interleukin-1β (IL-1β) pathway in cardiac diseases has also been more recognized. Methods We established a mice MI model which ligated with the left anterior descending coronary artery and a cardiomyocytes injury model treated by hydrogen peroxide (H2O2) to detect the expressions of miR-135b and NLRP3/caspase-1/IL-1β pathway. Then miR-135b mimic, agomir-135b, and α-MHC-miR-135b transgenic mice were used to evaluate the effects of miR-135b overexpression. Result We demonstrated that miR-135b was downregulated after cardiomyocytes injury both in vivo and in vitro. Pyroptosis pathway was also activated. MiR-135b overexpression remarkably restored impaired cardiac function and attenuated the upregulation of NLRP3/caspase-1/IL-1β pathway. Conclusions The present findings shed light on the protective role of miR-135b in MI mediated by the inhibition of the NLRP3/caspase-1/IL-1β pathway.

This study aimed to identify the change of cerebrospinal fluid (CSF) zinc-α2-glycoprotein (ZAG), tau protein and phosphorylated tau 181 (P-Tau 181), and analyze their association with white matter impairment (WMI) in patients with temporal lobe epilepsy (TLE). Levels of ZAG, tau, and P-Tau 181 in CSF were measured by enzyme-linked immunosorbent assay. WMI was scored based on Scheltens and Ylikoski scales. ZAG and total tau (T-Tau) were decreased in CSF of patients with TLE than controls (P

Narcolepsy is a sleep disorder with the main manifestations of excessive daytime sleepiness, cataplexy, sleep paralysis, sleep hallucinations, and nighttime sleep disturbance. It is still not fully recognized by clinicians, and many patients are often misdiagnosed with epilepsy, syncope, or mental disorders. In the present study, we report the first case of narcolepsy diagnosed at the district, with a complete medical history, objective examinations, and cerebrospinal fluid and hematological tests, but no cataplexy. Mutiple sleep latentcy test (MSLT) showed that the average sleep latency was 3.1 min, and abnormal REM sleep episodes were detected in 4 naps. The average REM latency was 1.3 min. We review the knowledge and researches on this disease in Mainland China in the past 10 years. Data from China in 2014 showed a significant increase in the incidence of narcolepsy in 2011 after the H1N1 epidemic in China in 2009. Despite the low incidence rate, diagnosis of narcolepsy is still confusing and needs clinicians' attention. Whether the incidence of narcolepsy may increase after covid19 remains to be observed. So far, there is no clear evidence to support immunotherapy. In conclusion, further studies are needed to verify more treatments and improve the patient's life quality.

Background Cardiac hypertrophy is a serious factor underlying heart failure. Although a large number of pathogenic genes have been identified, the underlying molecular mechanisms of cardiac hypertrophy are still poorly understood. MicroRNAs are a class of small non-coding RNAs which regulate their target genes at the post-transcriptional level. L-type calcium channels play important role in hypertrophic signaling pathways, and CACNA1C is encoded by L-type calcium channels. Here, we hypothesize that the overexpression of miR-135b can attenuate hypertrophy by targeting CACNA1C. Methods We test the functional involvement of miR-135b in cardiac hypertrophy model. In order to evaluate the effect of miR-135b in cardiac hypertrophy, miR-135b mimic, miR-135b agomir and α-MHC-miR-135b transgenic mice were used for the overexpression of miR-135b. Luciferase reporter assays were used to testify the binding of miR-135b to the CACNA1C 3′UTR. Results Our results revealed that in a pathological cardiac hypertrophy model, the expression of miR-135b was clearly downregulated. Hypertrophic marker genes were upregulated after the knockdown of miR-135b in vitro, while the overexpression of miR-135b attenuated hypertrophy. These results suggested that miR-135b may weaken hypertrophic signals. We then explored the mechanism of miR-135b in hypertrophy and identified that CACNA1C was a target gene for miR-135b. The overexpression of miR-135b attenuated cardiac hypertrophy by targeting CACNA1C. Conclusions Our studies revealed that miR-135b is a critical regulator of cardiomyocyte hypertrophy. Our findings may provide a novel strategy for the treatment of cardiac hypertrophy.

Clinical disagreement over antiplatelet (AP) resumption in patients with primary intracranial hemorrhage (ICH) has long existed. This meta-analysis aimed to evaluate the benefits of AP resumption on preventing ischemic or thromboembolic events against its risks of promoting ICH recurrence or hematoma expansion.All relevant articles published in Pubmed, EMBASE, the Cochrane Library, and Science Direct from January 1950 to March 2017 were sourced, and the combined relative risk (RR) was calculated.A total of 3648 articles were found, and after screening, 6 cohort studies including 1916 patients were included in this meta-analysis. AP resumption was associated with a decreased risk of ischemic or thromboembolic events (RR, 0.61; 95% confidence interval (CI), 0.48-0.79; P0.01). There was no significant difference in the risk of ICH recurrence or hematoma expansion between patients with or without AP resumption (RR, 0.84; 95% CI, 0.47-1.51; P=0.56).AP resumption in patients with primary ICH reduced the risk of ischemic or thromboembolic events, without significant increase of risk of ICH recurrence or hematoma expansion.

Model combination, often regarded as a key sub-field of ensemble learning, has been widely used in both academic research and industry applications. To facilitate this process, we propose and implement an easy-to-use Python toolkit, combo, to aggregate models and scores under various scenarios, including classification, clustering, and anomaly detection. In a nutshell, combo provides a unified and consistent way to combine both raw and pretrained models from popular machine learning libraries, e.g., scikit-learn, XGBoost, and LightGBM. With accessibility and robustness in mind, combo is designed with detailed documentation, interactive examples, continuous integration, code coverage, and maintainability check; it can be installed easily through Python Package Index (PyPI) or https://github.com/yzhao062/combo., In Proceedings of Thirty-Fourth AAAI Conference on Artificial Intelligence (AAAI 2020)

As a key component of Smart Grid, the smart Micro grid can integrate renewable energy source effectively and improve the quality of electric power on the demand side. Since the micro grid environment is complex and dynamic, how to achieve an optimal and state performance while improving the utility of electricity consumer in micro grid system is a crucial problem. To maximum the consumers' benefits and resource utilization while satisfying users' requests, it is essential for micro grid system and consumers to allocate resources adaptively for different conditions. In this paper, we proposed a dynamic developing power management framework in micro grid. A dynamic differential game model is modeled and analyzed to solve the optimization. The experiments results support a theoretical foundation that can help decision-maker make the optimal dynamic strategies when electricity consumer dynamically change their strategies.

As a new paradigm providing economic and low latency network, Fog computing can provide storage and computational capabilities to the electrical users. Since the Ubiquitous Smart Grid environment is complex and dynamic, it is an important problem for electrical provider to allocate the non-infinite electrical computing resources of nodes to reach an optimal and state performance. To maximum the benefits and resource utilization while satisfying users requests, it is essential for service provider to allocate resources adaptively for different conditions. In this paper, we propose a dynamic resource optimization allocation framework for the problem of Fog resource allocation for Ubiquitous Smart Grid. A dynamic differential game model is modeled and analyzed to solve the independent optimization. The experiments results support a theoretical foundation that can help service provider make the optimal dynamic strategies when users change their strategies.

// Baoyue Ding 1, 2, 3, * , Wei Zhang 4, * , Xin Wu 5, * , Jeffrey Wang 3 , Chen Xie 3 , Xuan Huang 1 , Shuyu Zhan 1 , Yongxia Zheng 1 , Yueyan Huang 1 , Ningyin Xu 1 , Xueying Ding 5 , Shen Gao 2 1 Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China 2 Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, PR China 3 Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, USA 4 Department of Pharmaceutics, Shanghai Pulmonary Hospital, Tongji University, Shanghai, PR China 5 Department of Pharmaceutics, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, PR China * These authors have contributed equally to this work Correspondence to: Shen Gao, email: liullk@126.com Xueying Ding, email: dingxueying@126.com Baoyue Ding, email: lena_310@163.com Keywords: malignant melanoma, DR5 monoclonal antibodies, dacarbazine, chemoimmunotherapy, active targeting nanoparticles Received: April 25, 2016 Accepted: July 19, 2016 Published: August 2, 2016 ABSTRACT We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR). In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment.

Aims: Within the past few years, there has been tremendous growth in clinical trials of chimeric antigen receptor (CAR) T-cell therapies. Unlike those of many small-molecule pharmaceuticals, CAR T-cell therapy clinical trials are fraught with risks due to the use of live cell products. The aim of this study is to reach a consensus with experts on the most relevant set of risks that practically occur in CAR T-cell therapy clinical trials. Methods: A Delphi method of consensus development was used to identify the risks in CAR T-cell therapy clinical trials, comprising three survey rounds. The expert panel consisted of principal investigators, clinical research physicians, members of institutional ethics committees, and Good Clinical Practice managers. Results: Of the 24 experts invited to participate in this Delphi study, 20 participants completed Round 1, Round 2, and Round 3. Finally, consensus (defined as >80% agreement) was achieved for 54 risks relating to CAR T-cell clinical trials. Effective interventions related to these risks are needed to ensure the proper protection of subject health and safety. Conclusion: The Delphi method was successful in gaining a consensus on risks relevant to CAR T-cell clinical trials in a geographically diverse expert association. It is hoped that this work can benefit future risk-based quality management in clinical trials and can potentially promote the better development of CAR T-cell therapy products.

Introduction Prolonged postoperative analgesia cannot be achieved by a single injection of local anesthetic solution. The objective of this study was to optimize the formulation of a ropivacaine hydrochloride (Ropi-HCl) loaded in situ forming implant (ISI) by addition of different co-solvents, and evaluate the in vitro release of Ropi-HCl, and the analgesic effect and toxicity of the optimized formulation in rats.

20(R)-ginsenoside Rg3 (20(R)-Rg3) has shown multiple pharmacological activities and been considered as one of the most promising approaches for fatigue treatment. However, 20(R)-Rg3 has a low bioavailability after oral administration in human due to the first-pass effect. Recently, nasal route has gained increasing interest as it can avoid first-pass effect for its lower enzymatic activity compared with the gastrointestinal tract and liver. In order to provide an animal experimental evidence of 20(R)-Rg3 intranasal administrated preparation, the anti-fatigue effect of 20(R)-Rg3 after intranasal administration was investigated. Two weeks after 20(R)-ginsenoside Rg3 was administrated intranasally to mice at three different doses, the anti-fatigue effect of 20(R)-Rg3 was evaluated by the weight-loaded swimming test and biochemical parameters related to fatigue, such as serum urea nitrogen (SUN), lactic dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), blood lactic acid (LA) and hepatic glycogen. The results showed that compared with the negative control group, the intermediate-dose and the high-dose groups significantly prolonged the weight-loaded swimming time (p